Drugs in space and sleepless in the shuttle

A fascinating study published in today’s Lancet Neurology reports on sleep deprivation in astronauts but also describes the drugs shuttle crew members use to keep themselves awake and help them fall asleep.

The study looked at sleep data from 64 astronauts on 80 space shuttle missions along with 21 astronauts on 13 International Space Station missions, and compared it to their sleep on the ground and in the days before space flight.

Essentially, in-flight astronauts don’t get a great deal of shut-eye, but what’s surprising is the range and extent of drugs they use to manipulate sleep.

Mostly these are the z-drug class of sleep medications (of which the best known is zolpidem, branded name Ambien) but also include benzos, melatonin and an antipsychotic called quetiapine.

Here are the sleep-inducing drugs with my comments in square brackets:

Zolpidem and zolpidem controlled release were the most frequently used drugs on shuttle missions, accounting for 301 (73%) and 49 (12%) of the 413 nights, respectively, when one dose of drug was reported. Zaleplon use was reported on 45 (11%) of 413 nights.

The paper also notes concerns about the astronauts’ use of zolpidem and similar z-drug medications because they can affect mental sharpness, coordination and can lead to unusual and complex ‘sleep-behaviours’.

Interestingly, it seems astronauts tend to use these drugs in a rather ad-hoc manner and the consequences of this have clearly not been well thought through.

As the Lancet Neurology paper notes:

This consideration is especially important because all crew members on a given mission might be taking a sleep-promoting drug at the same time…. crew members reported taking a second dose of hypnotic drugs—most commonly zolpidem—often only a few hours before awakening. Although crew members are encouraged to try such drugs on the ground at home at least once before their use in flight, such preparations probably do not involve multiple dosing or dosing with two different drugs on the same night.

Furthermore, such tests do not include any measure of objective effectiveness or safety, such as what would happen in the case of abrupt awakening during an in-flight night-time emergency… sleep-related-eating, sleep-walking, and sleep-driving events have been reported with zolpidem use, leading the FDA to require a so-called black-box warning on all hypnotic drugs stating that driving and performance of other tasks might be impaired in the morning after use of such drugs:

“A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of sedative/hypnotics…. Complex behaviors such as ‘sleep-driving’…have been reported. Amnesia, anxiety, and other neuropsychiatric symptoms may occur unpredictably.”

However, use of sleep drugs was reported on more than half the nights before extravehicular activities were undertaken.

Information on stimulant use by astronauts is hidden in the appendix but caffeine was widely used in space, but less than when on the ground – although possibly due to coffee shortages, and modafinil was used occasionally.

Caffeine was widely used throughout all data collection intervals by both shuttle and ISS crewmembers, though supply shortages sometimes led to coffee rationing and reduced consumption aboard ISS. All but eight shuttle mission crewmembers (72/80, 90%) and all but one ISS crewmember (20/21,95%) reported using caffeine at least once during the study…

Given the 3-7 hour half-life of caffeine and the sleep disturbances associated with its use, caffeine may have contributed to or enabled the sleep curtailment observed in this population. However, there is no evidence that caffeine accounts for the reduced sleep duration observed during spaceflight, as caffeine consumption was, if anything, reduced during spaceflight.

The wakefulness-promoting medication, modafinil, was reportedly used on both shuttle (10 reported uses) and ISS missions (2 reported uses). The use of this wakefulness-promoting medication was reported more frequently in post-flight debriefs.

There’s also an interesting snippet that gives the most common reason for sleep disturbance in space:

Nocturnal micturition is common in this age group and was the most reported reason for disruptive sleep both on Earth and inflight

Not stress, not being surrounded by equipment, not a lack of home comforts, but ‘Nocturnal micturition’ or wetting yourself in your sleep.

This is possibly more likely in space due to the fact that bodily cues for a full bladder work less effectively in zero gravity, but one major factor in astronauts wetting themselves was that it a better alternative than waking sleeping colleagues by going to the toilet.

The paper notes that this is why many astronauts wear ‘maximum absorbency garments’ – essentially giant nappies – while they sleep.

Wow, very interesting. I would think z-drugs would be a better choice than benzos b/c of the shorter half life (although they could go with something like zaleplon, with an even shorter half life than zolpidem) but I would also think if they were taking z-drugs they would have to do it in shifts b/c of the strange behavior that can occur when people take them. Benzos would probably cause more grogginess next day, but I don’t know which would be worse to have to wake up in the middle of (probably z-drugs) if something important was going on. It’s pretty crazy that more thought isn’t put into taking these drugs in-flight; I would think the astronauts themselves would be concerned enough about it to incorporate some safeguards.

Is characterizing nocturnal micturation as “wetting themselves” accurate? The sentence that you cite is referring to what happens on earth, and on earth, people in this age group often wake up in the night to use the bathroom rather than wet themselves.

Giving black box drugs to astronauts. That’s beautiful. Classic US government incompetence – they should put this on a postage stamp. I never understood the usefulness of black box warnings. “Here’s your prescription. It’s very risky. Don’t take it”! Some drugs like clindamycin have obviously done as much harm as good.